{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:56:10Z","timestamp":1780574170618,"version":"3.54.1"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,19]],"date-time":"2024-05-19T00:00:00Z","timestamp":1716076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>CHARGE syndrome, characterized by a distinct set of clinical features, has been linked primarily to mutations in the CHD7 gene. Initially defined by specific clinical criteria, including coloboma, heart defects, choanal atresia, delayed growth, and ear anomalies, CHARGE syndrome\u2019s diagnostic spectrum has broadened since the identification of CHD7. Variants in this gene exhibit considerable phenotypic variability, leading to the adoption of the term \u201cCHD7 disorder\u201d to encompass a wider range of associated symptoms. Recent research has identified CHD7 variants in individuals with isolated features such as autism spectrum disorder or gonadotropin-releasing hormone deficiency. In this study, we present three cases from two different families exhibiting audiovestibular impairment as the primary manifestation of a CHD7 variant. We discuss the expanding phenotypic variability observed in CHD7-related disorders, highlighting the importance of considering CHD7 in nonsyndromic hearing loss cases, especially when accompanied by inner ear malformations on MRI. Additionally, we underscore the necessity of genetic counseling and comprehensive clinical evaluation for individuals with CHD7 variants to ensure appropriate management of associated health concerns.<\/jats:p>","DOI":"10.3390\/genes15050643","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T11:06:41Z","timestamp":1716203201000},"page":"643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CHD7 Disorder\u2014Not CHARGE Syndrome\u2014Presenting as Isolated Cochleovestibular Dysfunction"],"prefix":"10.3390","volume":"15","author":[{"given":"Jef","family":"Driesen","sequence":"first","affiliation":[{"name":"Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Van Hoecke","sequence":"additional","affiliation":[{"name":"Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leen","family":"Maes","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences, Faculty of Medicine and Health Sciences, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Janssens","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Acke","sequence":"additional","affiliation":[{"name":"Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2789-3529","authenticated-orcid":false,"given":"Els","family":"De Leenheer","sequence":"additional","affiliation":[{"name":"Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0022-3476(81)80454-4","article-title":"Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association","volume":"99","author":"Pagon","year":"1981","journal-title":"J. Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1177\/000992289803700302","article-title":"CHARGE association: An update and review for the primary pediatrician","volume":"37","author":"Blake","year":"1998","journal-title":"Clin. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/ajmg.a.30559","article-title":"Updated diagnostic criteria for CHARGE syndrome: A proposal","volume":"133A","author":"Verloes","year":"2005","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/ng1407","article-title":"Mutations in a new member of the chromodomain gene family cause CHARGE syndrome","volume":"36","author":"Vissers","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1136\/jmg.2005.036061","article-title":"CHARGE syndrome: The phenotypic spectrum of mutations in the CHD7 gene","volume":"43","author":"Jongmans","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1002\/ajmg.a.33323","article-title":"Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome","volume":"152A","author":"Zentner","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1136\/jmg.2010.087106","article-title":"CHD7 mutations and CHARGE syndrome: The clinical implications of an expanding phenotype","volume":"48","author":"Bergman","year":"2011","journal-title":"J. Med. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11472","DOI":"10.1073\/pnas.94.21.11472","article-title":"Characterization of the CHD family of proteins","volume":"94","author":"Woodage","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.tig.2015.05.009","article-title":"Functional Insights into Chromatin Remodelling from Studies on CHARGE Syndrome","volume":"31","author":"Basson","year":"2015","journal-title":"Trends Genet. TIG"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"28847","DOI":"10.1073\/pnas.2005222117","article-title":"CHD7 regulates cardiovascular development through ATP-dependent and -independent activities","volume":"117","author":"Yan","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/ajmg.a.31921","article-title":"Familial CHARGE syndrome and the CHD7 gene: A recurrent missense mutation, intrafamilial recurrence and variability","volume":"146A","author":"Jongmans","year":"2008","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/ajmg.a.37435","article-title":"Atypical phenotypes associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria","volume":"170A","author":"Hale","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_13","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya , A. (1993). GeneReviews\u00ae [Internet], University of Washington. Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1117\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1002\/humu.22086","article-title":"Mutation update on the CHD7 gene involved in CHARGE syndrome","volume":"33","author":"Janssen","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ajhg.2013.06.012","article-title":"Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing","volume":"93","author":"Jiang","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/nature10989","article-title":"Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations","volume":"485","author":"Vives","year":"2012","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17953","DOI":"10.1073\/pnas.1417438111","article-title":"Functionally compromised CHD7 alleles in patients with isolated GnRH deficiency","volume":"111","author":"Balasubramanian","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/ajmg.a.36192","article-title":"Family history and clefting as major criteria for CHARGE syndrome","volume":"164A","author":"Hughes","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s00439-023-02581-x","article-title":"CHD7 variants associated with hearing loss and enlargement of the vestibular aqueduct","volume":"142","author":"Roux","year":"2023","journal-title":"Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1161\/CIRCGENETICS.113.000054","article-title":"The cardiac phenotype in patients with a CHD7 mutation","volume":"6","author":"Baardman","year":"2013","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e210522","DOI":"10.1530\/EC-21-0522","article-title":"Phenotypic spectrum of patients with mutations in CHD7: Clinical implications of endocrinological findings","volume":"11","author":"Kim","year":"2022","journal-title":"Endocr. Connect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/cge.12115","article-title":"Identification of two novel splice-site mutations in CHD7 gene in two patients with classical and atypical CHARGE syndrome phenotype","volume":"85","author":"Cappuccio","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"852429","DOI":"10.3389\/fgene.2022.852429","article-title":"Discovery of Novel Variants on the CHD7 Gene: A Case Series of CHARGE Syndrome","volume":"13","author":"Wu","year":"2022","journal-title":"Front. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Song, M.H., Cho, H.J., Lee, H.K., Kwon, T.J., Lee, W.S., Oh, S., Bok, J., Choi, J.Y., and Kim, U.K. (2011). CHD7 mutational analysis and clinical considerations for auditory rehabilitation in deaf patients with CHARGE syndrome. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024511"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.cell.2013.07.011","article-title":"Mechanisms and functions of ATP-dependent chromatin-remodeling enzymes","volume":"154","author":"Narlikar","year":"2013","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nn.4258","article-title":"Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination","volume":"19","author":"He","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/nature03487","article-title":"Sox2 is required for sensory organ development in the mammalian inner ear","volume":"434","author":"Kiernan","year":"2005","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"23293","DOI":"10.1038\/srep23293","article-title":"Sox2 in the differentiation of cochlear progenitor cells","volume":"6","author":"Kempfle","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.ydbio.2006.03.014","article-title":"Sox9 is required for notochord maintenance in mice","volume":"295","author":"Barrionuevo","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/nature08733","article-title":"CHD7 cooperates with PBAF to control multipotent neural crest formation","volume":"463","author":"Bajpai","year":"2010","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e1372","DOI":"10.1002\/mgg3.1372","article-title":"CHD7 missense variants and clinical characteristics of Chinese males with infertility","volume":"8","author":"Li","year":"2020","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref_32","first-page":"1055","article-title":"The chromatin remodeling protein CHD7, mutated in CHARGE syndrome, is necessary for proper craniofacial and tracheal development","volume":"243","author":"Sperry","year":"2014","journal-title":"Dev. Dyn. Off. Publ. Am. Assoc. Anat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7053","DOI":"10.1038\/s41467-022-34759-8","article-title":"CHD7 regulates otic lineage specification and hair cell differentiation in human inner ear organoids","volume":"13","author":"Nie","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/cne.21460","article-title":"Defects in vestibular sensory epithelia and innervation in mice with loss of Chd7 function: Implications for human CHARGE syndrome","volume":"504","author":"Adams","year":"2007","journal-title":"J. Comp. Neurol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/5\/643\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:44:45Z","timestamp":1760107485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/5\/643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,19]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["genes15050643"],"URL":"https:\/\/doi.org\/10.3390\/genes15050643","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,19]]}}}